Radiation Therapy as an Effective Salvage Strategy for Secondary CNS Lymphoma

Milgrom, Sarah A.; Pinnix, Chelsea C.; Linda, T.; Vu, Thinh; Gunther, Jillian R.; Sheu, Tommy; Fowler, Nathan; Westin, Jason R.; Nastoupil, Loretta J.; Oki, Yasuhiro; Fayad, Luis; Neelapu, Sattva S.; Rodriguez, Maria Alma; Hagemeister, Frederick; Fanale, Michelle A.; Lee, Hun J.; Hosing, Chitra; Ahmed, Sairah; Nieto, Yago; Shpall, Elizabeth J.; Dabaja, Bouthaina S.

doi:10.1016/j.ijrobp.2018.01.003

Cited by 12 publications

(10 citation statements)

References 18 publications

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“…Two observational series met inclusion criteria and were included in the study (Table 7) (74, 75). A total of 47 patients treated between 1988 and 2016 included diagnoses of chronic lymphocytic leukemia (CLL; n = 3) and diffuse large B-cell lymphoma (DLBCL; n = 44).…”

Section: Resultsmentioning

confidence: 99%

Radiotherapy in Leptomeningeal Disease: A Systematic Review of Randomized and Non-randomized Trials

Buszek

Chung

2019

Front. Oncol.

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Background: Leptomeningeal disease (LMD), also known as neoplastic meningitis, leptomeningeal carcinomatosis, or carcinomatous meningitis, is a rare cancer complication occurring in ~5% of cases and ultimately leads to significant morbidity and mortality. In the modern era, incidence of this condition continues to rise with longer survival of patients with advanced and even metastatic disease due to continued improvements in systemic therapies that are providing prolonged control of distant disease, but with limited effect in the central nervous system (CNS). Typical treatment strategies include optimal systemic therapy for the primary disease, as well as neuroaxis directed therapies, which may include intrathecal chemotherapy (ITC) or radiotherapy (RT).Methods: A systematic review of radiotherapy for LMD was performed. Medline, EMBASE, and Cochrane databases were searched from 1946 to 2018 for clinical trials, retrospective/prospective reviews, and case series with ≥2 human subjects that used radiation therapy techniques in the treatment of LMD. The outcome measures of interest included: characteristics of trial participants, inclusion/exclusion criteria, study type, number of participants, primary cancer histology, type of intervention for LMD, survival results if reported, length of follow up, and study conclusion.Results: Of 547 unique citations, 62 studies met the pre-specified eligibility criteria. These studies included 36 retrospective cohorts, 11 prospective series, 12 case series, and a single citation of guidelines, NCDB analysis, and a randomized control trial. Owing to study heterogeneity, meta-analyses of the endpoint data could not be performed.Conclusions: LMD is a devastating complication of cancer with reported survivals ranging from 2 to 4 months. Based on this systematic review, the recommendation for the treatment of LMD is for multimodality discussion of cases and treatment, including the use of radiotherapy, for LMD. However, with continued advances in systemic therapy as well as imaging advances, the landscape of LMD is evolving rapidly and the role of RT will likely also continue to evolve and advance. There is limited high-quality evidence to guide the optimal use of RT for the treatment of LMD, and there is a great need for prospective, histology specific investigation of the role of radiotherapy for LMD in the era of modern systemic therapies.

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Section: Resultsmentioning

confidence: 99%

Radiotherapy in Leptomeningeal Disease: A Systematic Review of Randomized and Non-randomized Trials

Buszek

Chung

2019

Front. Oncol.

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“…Our prior study of radiation as salvage therapy for patients with secondary CNS lymphoma has noted that progression after RT involved the CNS in only a minority of cases and systemic sites outside the CNS in the majority [8]. This was in contrast to outcomes in cohorts of patients treated with high dose CT and SCT without RT, such as in a study in which patients were treated with methotrexate, CT, and SCT, in which the vast majority of patients relapsed in the CNS [13].…”

Section: Discussionmentioning

confidence: 99%

“…Achieving CNS disease remission prior to SCT is critical for achieving extended disease remission [7]. Radiation therapy (RT) has been identified as a potentially effective salvage strategy for secondary CNS lymphoma [8]. However, it is unclear which cohorts of patients may derive the most benefit from radiation compared to other treatments, and whether there are underlying factors such as CNS disease distribution, pathology or patient characteristics that may identify patients who are most likely to successfully respond and be bridged to consolidation with stem cell transplant or other therapies.…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of disease distribution in secondary central nervous system diffuse large B cell lymphoma treated with radiation therapy

Feghali

Fang

Gule-Monroe

et al. 2021

Leukemia & Lymphoma

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This study aimed to assess the prognostic value of baseline disease distribution for patients with the secondary central nervous system (CNS) diffuse large B-cell lymphoma (DLBCL) treated with chemotherapy and radiation (RT). 44 patients with secondary CNS DLBCL were reviewed. Twenty patients had leptomeningeal disease (LMD), and 24 had localized/targetable disease (LTD). Of 8 patients who received stem cell transplantation (SCT) after RT, 6 had LTD with a complete or partial response after RT. Median time to CNS relapse after RT was 10.1 months; 3/24 patients with LTD and 5/15 with LMD had CNS relapse. The median overall survival (OS) was 8 and 20 months for patients with LMD and LTD, respectively (p ¼ 0.20). On multivariable analysis, LTD, receipt of SCT, and response after RT were associated with better OS and CNS-disease-free survival. Patients with localized secondary CNS DLBCL may benefit from RT serving as a bridge to SCT.

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“…(52) As salvage therapy in SCNSL, earlier retrospective series showed responses in 67% -88% of patients including ~50% achieving CR with a 2-year OS of ~ 30%. (72,73) A retrospective study of 44 patients reported that the dominant pattern of relapse after RT was with systemic disease (n=18) and that outcomes were more favourable in patients receiving consolidation with ASCT after RT (n=8). (72) Neurotoxicity represents the major long-term complication after WBRT in long-lasting survivors particularly in those > 60 years with PCNSL.…”

Section: Role Of Radiation Therapymentioning

confidence: 99%

“…(72,73) A retrospective study of 44 patients reported that the dominant pattern of relapse after RT was with systemic disease (n=18) and that outcomes were more favourable in patients receiving consolidation with ASCT after RT (n=8). (72) Neurotoxicity represents the major long-term complication after WBRT in long-lasting survivors particularly in those > 60 years with PCNSL. Importantly, the PRECIS study, conducted in patients <60 years with PCNSL, showed significant neurocognitive decline during follow up in patients randomized to WBRT consolidation using doses of 40Gy compared to those receiving a ASCT (64% v 13%, P < .001).…”

Section: Role Of Radiation Therapymentioning

confidence: 99%

Prevention and management of secondary central nervous system lymphoma

et al. 2022

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Secondary central nervous system (CNS) lymphoma (SCNSL) is defined by the involvement of the CNS, either at the time of initial diagnosis of systemic lymphoma, or in the setting of relapse, either isolated or with synchronous systemic disease. The risk of CNS involvement in patients with diffuse large B-cell lymphoma is approximately 5%, however, certain clinical and biological features have been associated with a risk of up to 15%. There has been growing interest in improving the definition of patients at increased risk of CNS relapse, as well as identifying effective prophylactic strategies to prevent it. SCNSL often occurs within months of initial lymphoma diagnosis, suggesting presence of occult disease at diagnosis in many cases. The differing presentations of SCNSL present a therapeutic challenge of control of both systemic disease and CNS disease, which uniquely requires agents that penetrate the blood brain barrier. Outcomes are generally poor with a median overall survival of approximately 6 months in retrospective series, particularly those presenting with SCNSL after prior therapy. Prospective studies of intensive chemotherapies containing high-dose methotrexate (HD-MTX), followed by haematopoietic stem cell transplantation have shown the most favourable outcomes, especially for patients receiving thiotepa-based conditioning regimens. However, a proportion of patients will not respond to induction therapies or subsequently relapse, indicating the need for more effective treatment strategies. In this review we focus on the identification of high-risk patients, prophylaxis strategies and recent treatment approaches for SCNSL. The incorporation of novel agents to immunochemotherapy deserves further study in prospective trials.

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Radiation Therapy as an Effective Salvage Strategy for Secondary CNS Lymphoma

Cited by 12 publications

References 18 publications

Radiotherapy in Leptomeningeal Disease: A Systematic Review of Randomized and Non-randomized Trials

Radiotherapy in Leptomeningeal Disease: A Systematic Review of Randomized and Non-randomized Trials

Prognostic value of disease distribution in secondary central nervous system diffuse large B cell lymphoma treated with radiation therapy

Prevention and management of secondary central nervous system lymphoma

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